Conditioning lesions of peripheral nerves change regenerated axon numbers

The present study investigates the effects of conditioning lesions on regenerated axon numbers in tributary nerves after a test lesion. If a rat sciatic nerve is crushed 7 and 14 days prior to a test crush, the numbers of regenerated myelinated axons 8 weeks later in the sural nerve (SN) and nerve to the medial gastrocnemius (NMG) are increased, both over normal and over numbers after a single crush. If the lesions are only separated by 2 days, however, the numbers are similar to the numbers after a single crush. Thus conditioning occurs, but a minimum time between crushes is necessary for the effects of conditioning to be manifest. If the intervals between lesions are 14 days, the numbers are similar to those after the 7-day intervals. Moving each successive crush proximally or distally does not change regenerated myelinated axon numbers. Thus increasing the time between lesions after conditioning occurs, at least within the constraints of our paradigm, does not change regenerated axon numbers and the location of the lesion has relatively little bearing on the numbers of axons that regenerate. These findings allow us to change axonal numbers in these tributary nerves in a predictable way, and they are also compatible with the hypothesis that conditioning results from priming of the cell body rather than changes in the environment of the regenerating axons.